title: Exposure of Thomsen-Friedenreich antigen in Streptococcus pneumoniae infection is dependent on pneumococcal neuraminidase A.
abstract: Pneumococcal hemolytic uremic syndrome is recognized in a small portion of otherwise healthy children who have or have recently had Streptococcus pneumoniae infections, including severe pneumonia, meningitis, and bacteremia. As in other types of hemolytic uremic syndrome (HUS), pneumococcal HUS is characterized by microangiopathic hemolytic anemia, and thrombocytopenia, usually with extensive kidney damage. Although not demonstrated in vivo, the pathogenesis of pneumococcal HUS has been attributed to the action pneumococcal neuraminidase exposing the usually cryptic Thomsen-Friedenreich antigen (T-antigen) on red blood cells (RBC), and kidney glomeruli. We evaluated the effect of pneumococcal infection on desialylation of RBC and glomeruli during pneumococcal infections in mice. Following intravenous infection with capsular type 19F pneumococci, CFU levels exceeding 1000 CFU/mL blood by the third day were significantly more likely to result in exposed T-antigen on RBC than lower levels of bacteremia. In a pneumonia model, significantly more T-antigen was exposed on RBC in mice treated with penicillin than in those receiving mock treatment. Utilizing mutant pneumococci, we demonstrated that neuraminidase A but not neuraminidase B was necessary for exposure of T-antigen on RBC in vivo. Thus, pneumococcal neuraminidase A is necessary for the exposure of T-antigen in vivo and treatment with penicillin increases this effect. Interestingly, NanA(-) pneumococci were found in the blood in higher numbers and caused more deaths than wild type, NanB(-), or the NanA(-)/NanB(-) pneumococci.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 1530 3rd Ave South, Birmingham, AL 35294-2170, USA.
authors.forename: Mamie T
authors.initials: MT
authors.lastname: Coats
authors.forename: Trudy
authors.initials: T
authors.lastname: Murphy
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Barry
authors.initials: B
authors.lastname: Gray
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000097:blood / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000276:immunology / Q000382:microbiology; D007668:Kidney / Q000201:enzymology / Q000276:immunology; D008586:Meningitis, Pneumococcal / Q000097:blood / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008808:Mice, Inbred CBA; D009439:Neuraminidase / Q000172:deficiency / Q000276:immunology*; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000097:blood / Q000276:immunology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000276:immunology*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000957:Antigens, Viral, Tumor; C016467:Thomsen-Friedenreich antigen; D009439:Neuraminidase